Coding region: Difference between revisions

Revision as of 15:21, 17 March 2020

Revision as of 07:54, 12 April 2020

Line 13:

== Composition ==

[[File:Transitions-transversions.png|thumb|286x286px|'''Point mutation types:''' transitions (blue) are elevated compared to transversions (red) in GC-rich coding regions.<ref>(n.d.). Retrieved from <nowiki>https://www.differencebetween.com/wp-content/uploads/2017/03/Difference-Between-Transition-and-Transversion-3.png</nowiki></ref>]]

The evidence suggests that there is a general interdependence between base composition patterns and coding region availability.<ref>{{cite journal | vauthors = Lercher MJ, Urrutia AO, Pavlícek A, Hurst LD | title = A unification of mosaic structures in the human genome | journal = Human Molecular Genetics | volume = 12 | issue = 19 | pages = 2411–5 | date = October 2003 | pmid = 12915446 | doi = 10.1093/hmg/ddg251 | doi-access = free }}</ref> The coding region is thought to contain a higher [[GC-content]] than non-coding regions. There is further research that discovered that the longer the coding strand, the higher the GC-content. Short coding strands are comparatively still GC-poor, similar to the low GC-content of the base composition translational [[stop codon]]s like TAG, TAA, and TGA.<ref>{{cite journal | vauthors = Oliver JL, Marín A | title = A relationship between GC content and coding-sequence length | journal = Journal of Molecular Evolution | volume = 43 | issue = 3 | pages = 216–23 | date = September 1996 | pmid = 8703087 | doi = 10.1007/pl00006080 | bibcode = 1996JMolE..43..216O }}</ref>

GC-rich areas are also where the ratio [[point mutation]] type is altered slightly: there are more [[Transition (genetics)|transitions]], which are changes from purine to purine or pyrimidine to pyrimidine, compared to [[transversion]]s, which are changes from purine to pyrimidine or pyrimidine to purine. The transitions are less likely to change the encoded amino acid and remain a [[silent mutation]] (especially if they occur in the third [[nucleotide]] of a codon) which is usually beneficial to the organism during translation and protein formation.<ref>{{Cite web|url=http://rosalind.info/glossary/gene-coding-region/|title=ROSALIND {{!}} Glossary {{!}} Gene coding region|website=rosalind.info|access-date=2019-10-31}}</ref>

This indicates that essential coding regions (gene-rich) are higher in GC-content and more stable and resistant to [[mutation]] compared to accessory and non-essential regions (gene-poor).<ref>{{cite journal | vauthors = Vinogradov AE | title = DNA helix: the importance of being GC-rich | journal = Nucleic Acids Research | volume = 31 | issue = 7 | pages = 1838–44 | date = April 2003 | pmid = 12654999 | pmc = 152811 | doi = 10.1093/nar/gkg296 }}</ref> However, it is still unclear whether this came about through neutral and random mutation or through a pattern of [[Natural selection|selection]].<ref>{{cite journal | vauthors = Bohlin J, Eldholm V, Pettersson JH, Brynildsrud O, Snipen L | title = The nucleotide composition of microbial genomes indicates differential patterns of selection on core and accessory genomes | journal = BMC Genomics | volume = 18 | issue = 1 | pages = 151 | date = February 2017 | pmid = 28187704 | pmc = 5303225 | doi = 10.1186/s12864-017-3543-7 }}</ref> There is also debate on whether the methods used, such as gene windows, to ascertain the relationship between GC-content and coding region are accurate and unbiased.<ref>{{cite journal | vauthors = Sémon M, Mouchiroud D, Duret L | title = Relationship between gene expression and GC-content in mammals: statistical significance and biological relevance | journal = Human Molecular Genetics | volume = 14 | issue = 3 | pages = 421–7 | date = February 2005 | pmid = 15590696 | doi = 10.1093/hmg/ddi038 | doi-access = free }}</ref>

== Structure and Function ==

Line 31:

[[Alkylation]] is one form of regulation of the coding region.<ref>{{cite journal | vauthors = Shinohara K, Sasaki S, Minoshima M, Bando T, Sugiyama H | title = Alkylation of template strand of coding region causes effective gene silencing | journal = Nucleic Acids Research | volume = 34 | issue = 4 | pages = 1189–95 | date = 2006-02-13 | pmid = 16500890 | pmc = 1383623 | doi = 10.1093/nar/gkl005 }}</ref> The gene that would have been transcribed can be silenced by targeting a specific sequence. The bases in this sequence would be blocked using [[Alkyl|alkyl groups]], which create the [[Gene silencing|silencing]] effect.<ref>{{Cite web|url=http://www.informatics.jax.org/vocab/gene_ontology/GO:0006305|title=DNA alkylation Gene Ontology Term (GO:0006305)|website=www.informatics.jax.org|access-date=2019-10-30}}</ref>

While the [[regulation of gene expression]] manages the abundance of RNA or protein made in a cell, the regulation of these mechanisms can be controlled by a [[regulatory sequence]] found before the [[open reading frame]] begins in a strand of DNA. The [[regulatory sequence]] will then determine the ___location and time that expression will occur for a protein coding region.<ref>{{Cite journal |last1=Shafee|first1=Thomas|last2=Lowe|first2=Rohan | name-list-format = vanc |date=2017 |title=Eukaryotic and prokaryotic gene structure|journal=WikiJournal of Medicine|volume=4|issue=1|doi=10.15347/wjm/2017.002|doi-access=free}}</ref>

[[RNA splicing]] ultimately determines what part of the sequence becomes translated and expressed, and this process involves cutting out introns and putting together exons. Where the RNA [[spliceosome]] cuts, however, is guided by the recognition of [[splice site]]s, in particular the 5' splicing site, which is one of the substrates for the first step in splicing.<ref>{{cite journal | vauthors = Konarska MM | title = Recognition of the 5' splice site by the spliceosome | journal = Acta Biochimica Polonica | volume = 45 | issue = 4 | pages = 869–81 | date = 1998 | pmid = 10397335 | doi = 10.18388/abp.1998_4346 | doi-access = free }}</ref> The coding regions are within the exons, which become covalently joined together to form the [[mature messenger RNA]].

== Mutations ==

Line 54:

While identification of [[open reading frames]] within a DNA sequence is straightforward, identifying coding sequences is not, because the cell translates only a subset of all open reading frames to proteins.<ref>{{cite journal | vauthors = Furuno M, Kasukawa T, Saito R, Adachi J, Suzuki H, Baldarelli R, Hayashizaki Y, Okazaki Y | display-authors = 6 | title = CDS annotation in full-length cDNA sequence | journal = Genome Research | volume = 13 | issue = 6B | pages = 1478–87 | date = June 2003 | pmid = 12819146 | pmc = 403693 | doi = 10.1101/gr.1060303 | url = http://genome.cshlp.org/content/13/6b/1478.full.pdf+html | publisher = Cold Spring Harbor Laboratory Press }}</ref> Currently CDS prediction uses sampling and sequencing of mRNA from cells, although there is still the problem of determining which parts of a given mRNA are actually translated to protein. CDS prediction is a subset of [[gene prediction]], the latter also including prediction of DNA sequences that code not only for protein but also for other functional elements such as RNA genes and regulatory sequences.

In both [[prokaryote]]s and [[eukaryote]]s, [[Overlapping gene|gene overlapping]] occurs relatively often in both DNA and RNA viruses as an evolutionary advantage to reduce genome size while retaining the ability to produce various proteins from the available coding regions.<ref>{{cite journal | vauthors = Rogozin IB, Spiridonov AN, Sorokin AV, Wolf YI, Jordan IK, Tatusov RL, Koonin EV | title = Purifying and directional selection in overlapping prokaryotic genes | language = English | journal = Trends in Genetics | volume = 18 | issue = 5 | pages = 228–32 | date = May 2002 | pmid = 12047938 | doi = 10.1016/S0168-9525(02)02649-5 | url = https://www.cell.com/trends/genetics/abstract/S0168-9525(02)02649-5 }}</ref><ref>{{cite journal | vauthors = Chirico N, Vianelli A, Belshaw R | title = Why genes overlap in viruses | journal = Proceedings. Biological Sciences | volume = 277 | issue = 1701 | pages = 3809–17 | date = December 2010 | pmid = 20610432 | pmc = 2992710 | doi = 10.1098/rspb.2010.1052 }}</ref> For both DNA and RNA, [[Sequence alignment#Pairwise alignment|pairwise alignments]] can detect overlapping coding regions, including short [[open reading frame]]s in viruses, but would require a known coding strand to compare the potential overlapping coding strand with.<ref>{{cite journal | vauthors = Firth AE, Brown CM | title = Detecting overlapping coding sequences with pairwise alignments | journal = Bioinformatics | volume = 21 | issue = 3 | pages = 282–92 | date = February 2005 | pmid = 15347574 | doi = 10.1093/bioinformatics/bti007 | url = https://academic.oup.com/bioinformatics/article/21/3/282/237775 | doi-access = free }}</ref> An alternative method using single genome sequences would not require multiple genome sequences to execute comparisons but would require at least 50 nucleotides overlapping in order to be sensitive.<ref>{{cite journal | vauthors = Schlub TE, Buchmann JP, Holmes EC | title = A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences | journal = Molecular Biology and Evolution | volume = 35 | issue = 10 | pages = 2572–2581 | date = October 2018 | pmid = 30099499 | pmc = 6188560 | doi = 10.1093/molbev/msy155 | editor-first = Harmit | editor-last = Malik }}</ref>

== See also ==